A longitudinal study of polysomnographic variables in patients with mild cognitive impairment converting to Alzheimer's disease.

The main condition at increased risk of dementia is considered to be mild cognitive impairment. Mild cognitive impairment has been defined as a transitional state between normal aging and dementia, of which it may represent a prodrome. The aim of our study was to evaluate whether sleep variables (both conventional and microstructural ones) in subjects with mild cognitive impairment correlate with conversion to dementia. Nineteen subjects with amnestic mild cognitive impairment (mean age 68.5 ±â€…7.0 years) and 11 cognitively intact healthy elderly individuals (mean age 69.2 ±â€…12.6 years) underwent ambulatory polysomnography for the evaluation of nocturnal sleep architecture and cyclic alternating pattern parameters. Amnestic mild cognitive impairment subjects were clinically and cognitively re-evaluated after 2 years, during routine follow-up, and further classified as amnestic mild cognitive impairment converters (that is, patients developing Alzheimer's disease, N = 11) and amnestic mild cognitive impairment non-converters. Compared with healthy elderly individuals, amnestic mild cognitive impairment showed disrupted sleep with decreased rapid eye movement sleep, cyclic alternating pattern rate and cyclic alternating pattern slow-wave-related phases (A1 index). Standard sleep architecture analysis did not show significant differences between the two subgroups of amnestic mild cognitive impairment, whereas cyclic alternating pattern analysis showed that cyclic alternating pattern rate, A1 index and A3 index are significantly reduced in converters compared with non-converters. Our data confirm that in amnestic mild cognitive impairment subjects there is a sleep impairment, particularly when considering more refined sleep parameters and that sleep variables at baseline are different among converters versus non-converters at the 2-year follow-up. Specific sleep alterations might represent potential further biomarkers for the diagnosis and prognosis of early-phase cognitive impairment.

Relationship quality of persons with obstructive sleep apnoea syndrome.

In the field of sleep disorders, the quality of couple relationship is arousing increasing attention, given its implications for quality of life and treatment adherence. The aim of the present study was to evaluate relationship quality in a sample of treated or untreated patients with Obstructive Sleep Apnoea Syndrome. Eighty-seven patients were recruited in a hospital-based Centre for Sleep Medicine. Subjects were administered the Dyadic Adjustment Scale (DAS) to evaluate relationship quality, and the Epworth Sleepiness Scale (ESS). Apnoea-hypopnoea indexes (AHI) were collected through nocturnal polysomnography or home testing with a portable monitoring device. Although the DAS average scores were similar to local normative values, relationship quality was significantly lower in the untreated patients when compared with the ones treated. The ESS scores showed a negative correlation with many DAS scores, whereas no significant correlation emerged for AHI. Such data suggest a significant impact of perceived sleep apnoea symptoms on marital satisfaction, even though in the absence of striking differences between the whole sample and the general population.

Psychological well-being of patients with insomnia and its relationship with anxiety and depression.

The aims of the present study are to evaluate the impact of insomnia on psychological well-being and to examine the associations of insomnia and psychological well-being with anxiety and depression. Forty-one patients attending our hospital-based Centre for sleep medicine were administered scales for the evaluation of insomnia (ISI), anxiety (STAI-Y), depression (BDI-II) and psychological well-being (PWB). The scores were compared to those of a control group of 68 subjects attending the hospital for routine examinations or as accompanying persons. Significant differences between patients and controls were detected for anxiety and depression, as well as for psychological well-being. Even if subclinical on average, anxiety and depression symptoms were significantly related to poor psychological well-being, whereas insomnia per se was not. These findings suggest that patients with insomnia report a relevant impact on their psychological well-being, and that such an impact seems to be strongly associated with concomitant subthreshold symptoms of anxiety and depression. The implications for diagnosis and treatment are discussed.

Non-rapid eye movement sleep instability in mild cognitive impairment: a pilot study.

OBJECTIVE: Polysomnographic (PSG) studies in mild cognitive impairment (MCI) are not conclusive and are limited only to conventional sleep parameters. The aim of our study was to evaluate sleep architecture and cyclic alternating pattern (CAP) parameters in subjects with MCI, and to assess their eventual correlation with cognition. METHODS: Eleven subjects with MCI (mean age 68.5 ± 7.0 years), 11 patients with mild probable Alzheimer's disease (AD; mean age 72.7 ± 5.9 years), referred to the Outpatient Cognitive Disorders Clinic, and 11 cognitively intact healthy elderly individuals (mean age 69.2 ± 12.6 years) underwent ambulatory PSG for the evaluation of nocturnal sleep architecture and CAP parameters. RESULTS: Rapid eye movement sleep, CAP rate, and CAP slow components (A1 index) were decreased in MCI subjects and to a greater extent in AD patients, compared to cognitively intact controls. AD showed also decreased slow wave sleep (SWS) relative to healthy elderly individuals. MCI nappers showed decreased nocturnal SWS and A1 subtypes compared to non-nappers. Several correlations between sleep variables and neuropsychological tests were found. CONCLUSIONS: MCI and AD subjects showed a decreased sleep instability correlated with their cognitive decline. Such a decrease may be considered as a potential biomarker of underlying neurodegeneration.

NREM sleep transient events in fronto-temporal dementia: beyond sleep stage architecture.

Frontotemporal dementia (FTD) is increasingly becoming recognized as a major cause of early onset (<65 years) neurodegenerative dementia. Although sleep disorders significantly impair patients' and caregivers' quality of life in neurodegenerative diseases, polysomnographic data in FTD patients are scarce in literature. Aim of our study was to investigate sleep microstructure in FTD, by means of Cyclic Alternating Pattern (CAP), in a group of ten behavioral variant FTD patients (6 M, 4 F; mean age 61.2±7.3 years; disease duration: 1.4±0.7 years) and to compare them with cognitively intact healthy elderly. Sleep in FTD patients was altered at different levels, involving not only the conventional sleep stage architecture parameters (total sleep time, single stage percentage, NREM/REM cycle organization), but also microstructure. FTD subjects showed CAP disruption with decreased slow wave activity related phases (A1 index, n/h:14.5±6.8 vs 38.8±6.6; p<.001) and increased arousal-related fast CAP components (A2 index 22.9±8.2 vs 11.6±3.7; p=.006; A3 index 41.9±20.7 vs 13.0±6.5; p=.002). Several correlations between sleep variables and neuropsychological tests were found. Sleep impairment in FTD may be specifically related to the specific frontal lobe involvement in the neurodegenerative process. The pattern of alterations seems somewhat peculiar, probably due to the anatomical distribution of the neurodegenerative process with a major impact on frontal lobe generated sleep transients, and a substantial sparing of phenomena related to the posterior cortex.

Sleep in frontotemporal dementia is equally or possibly more disrupted, and at an earlier stage, when compared to sleep in Alzheimer's disease.

BACKGROUND: Conversely to other neurodegenerative diseases (i.e., Alzheimer's disease, AD), sleep in frontotemporal dementia (FTD) has not been studied adequately. Although some evidence exists that sleep-wake disturbances occur in FTD, very little is known regarding sleep macrostructure and/or primary sleep disorders. OBJECTIVE: To investigate these issues in this population and compare them to similar issues in AD and in healthy elderly (HE). METHODS: Twelve drug-naïve behavioral-variant FTD (bvFTD) patients (7 men/5 women) of mean age 62.5 ± 8.6 years were compared to seventeen drug-naïve AD patients (8 men/9 women) of mean age 69.0 ± 9.9 years and twenty drug-naïve HE (12 men/8 women) of mean age 70.2 ± 12.5 years. All participants were fully assessed clinically, through a sleep questionnaire, an interview, and video-polysomnography recordings. RESULTS: The two patient groups were comparably cognitively impaired. However, compared to FTD patients, the AD patients had a statistically significant longer disease duration. Overall, the sleep profile was better preserved in HE. Sleep complaints did not differ considerably between the two patient groups. Sleep parameters and sleep macrostructure were better preserved in AD compared to FTD patients, regardless of primary sleep disorders, which occurred equally in the two groups. CONCLUSIONS: With respect to AD, FTD patients had several sleep parameters similarly or even more affected by neurodegeneration, but in a much shorter time span. The findings probably indicate a centrally originating sleep deregulation. Since in FTD patients sleep disturbances may be obvious from an early stage of their disease, and possibly earlier than in AD patients, physicians and caregivers should be alert for the early detection and treatment of these symptoms.

A Clinical-EEG Study of Sleepiness and Psychological Symptoms in Pharmacoresistant Epilepsy Patients Treated with Lacosamide.

Our aim was to evaluate the EEG and clinical modifications induced by the new antiepileptic drug lacosamide (LCM) in patients with epilepsy. We evaluated 10 patients affected by focal pharmacoresistant epilepsy in which LCM (mean 250 mg/day) was added to the preexisting antiepileptic therapy, which was left unmodified. Morning waking EEG recording was performed before (t0) and at 6 months (t1) after starting LCM. At t0 and t1, patients were also administered questionnaires evaluating mood, anxiety, sleep, sleepiness, and fatigue (Beck Depression Inventory; State-Trait Anxiety Inventory Y1 and Y2; Pittsburgh Sleep Quality Index; Epworth Sleepiness Scale; Fatigue Severity Scale). We performed a quantitative analysis of EEG interictal abnormalities and background EEG power spectrum analysis. LCM as an add-on did not significantly affect anxiety, depression, sleepiness, sleep quality, and fatigue scales. Similarly, adding LCM to preexisting therapy did not modify significantly patient EEGs in terms of absolute power, relative power, mean frequency, and interictal abnormalities occurrence. In conclusion, in this small cohort of patients, we confirmed that LCM as an add-on does not affect subjective parameters which play a role, among others, in therapy tolerability, and our clinical impression was further supported by evaluation of EEG spectral analysis.

Daytime sleepiness in de novo untreated patients with epilepsy.

The aims of our study were to evaluate excessive daytime sleepiness in a group of de novo untreated people with epilepsy using a comprehensive and standardized approach, including subjective evaluation and neurophysiological and performance tests, and to compare these results with those obtained in a control group. Forty-seven patients with epilepsy (17 affected by primary generalized epilepsy and 30 by partial epilepsy), with a new epilepsy diagnosis and never treated, and 44 controls underwent Multiple Sleep Latency Test (preceded by nocturnal polysomnography), simple/complex visual reaction times, and Epworth Sleepiness Scale evaluation. Newly diagnosed and drug-free patients with epilepsy did not differ from controls in any of the tests performed to evaluate daytime sleepiness. In clinical practice, daytime sleepiness is a well-known and frequent complaint of patients with epilepsy, but different mechanisms and causes, such as associated psychiatric or sleep disorders, nocturnal seizures, sleep fragmentation, and antiepileptic drugs, must be taken into account. Excessive daytime sleepiness should not be considered an unavoidable consequence of epilepsy. Thus, a complete diagnostic work-up in patients with epilepsy and sleepiness should be undertaken whenever possible.

Renal vasodilating capacity and endothelial function are impaired in patients with obstructive sleep apnea syndrome and no traditional cardiovascular risk factors.

OBJECTIVE: Patients with obstructive sleep apnea syndrome exhibit accelerated vascular aging and renal damage. Aim of the study was to investigate whether vascular dysfunction is a feature of obstructive sleep apnea syndrome per se or instead related to the presence of traditional cardiovascular risk factors. METHODS: Forty patients with moderate-severe obstructive sleep apnea syndrome (20 with, 20 without traditional risk factors) and 20 matched healthy controls were enrolled. Renal vasodilating capacity, endothelium-dependent vasodilation in the brachial artery, carotid-femoral pulse wave velocity and carotid stiffness were measured. Oxidative stress, endothelial biomarkers and leukocyte adhesion molecule levels were also evaluated. RESULTS: Apneic patients without traditional cardiovascular risk factors presented reduced endothelium-dependent vasodilation (3.7±2.1 versus 6.1±3.0%, P<0.05), increased serum E-selectin (49.8±11.5 versus 38.9±17.9 ng/ml, P<0.05), and impaired renal vasodilating capacity (6.0±4.3 versus 10.4±6.1%, P<0.05), as compared to healthy controls. Endothelial NO synthase expression was reduced (0.0133 versus 0.0221×10 copies/µg RNA, P<0.05), whereas oxidative stress parameters and leukocyte adhesion molecules were similar to controls. Patients with obstructive sleep apnea syndrome and traditional risk factors also exhibit increased aortic and carotid stiffness, increased renal resistive index and intima-media thickness, and reduced expression of the endothelial progenitor cell marker CD34: however, these parameters were similar to those of healthy controls in patients with isolated obstructive sleep apnea syndrome. CONCLUSION: Obstructive sleep apnea syndrome is characterized by endothelial dysfunction and activation and impaired renal vasodilating capacity even in the absence of traditional cardiovascular risk factors, possibly due to reduced endothelial NO synthase expression.

Controversial issues on EEG after sleep deprivation for the diagnosis of epilepsy.

EEG after sleep deprivation (SD-EEG) is widely used in many epilepsy centers as an important tool in the epilepsy diagnosis process. However, after more than 40 years of use, there are a number of issues which still need to be clarified concerning its features and role. In particular, the many scientific papers addressing its role in epilepsy diagnosis often differ remarkably from each other in terms of the type of patients assessed, their description and study design. Furthermore, also the length and the type of EEG performed after SD, as well as the length of SD itself, vary dramatically from one study to another. In this paper we shortly underscore the abovementioned differences among the different reports, as well as some interpretations of the findings obtained in the different studies. This analysis emphasizes, if needed, how SD-EEG still represents a crucial step in epilepsy diagnosis, and how additional, controlled studies might further shape its precise diagnostic/prognostic role.

Differences in EEG delta frequency characteristics and patterns in slow-wave sleep between dementia patients and controls: a pilot study.

PURPOSE: To evaluate the modifications of EEG activity during slow-wave sleep in patients with dementia compared with healthy elderly subjects, using spectral analysis and period-amplitude analysis. METHODS: Five patients with dementia and 5 elderly control subjects underwent night polysomnographic recordings. For each of the first three nonrapid eye movement-rapid eye movement sleep cycles, a well-defined slow-wave sleep portion was chosen. The delta frequency band (0.4-3.6 Hz) in these portions was analyzed with both spectral analysis and period-amplitude analysis. RESULTS: Spectral analysis showed an increase in the delta band power in the dementia group, with a decrease across the night observed only in the control group. For the dementia group, period-amplitude analysis showed a decrease in well-defined delta waves of frequency lower than 1.6 Hz and an increase in such waves of frequency higher than 2 Hz, in incidence and amplitude. CONCLUSIONS: Our study showed (1) a loss of the dynamics of delta band power across the night sleep, in dementia, and (2) a different distribution of delta waves during slow-wave sleep in dementia compared with control subjects. This kind of computer-based analysis can highlight the presence of a pathologic delta activity during slow-wave sleep in dementia and may support the hypothesis of a dynamic interaction between sleep alteration and cognitive decline.

Insulinoma presenting as idiopathic hypersomnia.

We report the case of a 32-year-old woman with a history of increased sleep need and difficulty waking up; the diagnosis of idiopathic hypersomnia was hypothesized. During ambulatory polysomnography (PSG), the patient presented an episode characterized by loss of consciousness and jerking of the four limbs. A video-PSG monitoring was performed and the patient showed unresponsiveness and drowsiness at 7 a.m. During the episode, EEG showed theta-delta diffuse activity, and blood glucose level was 32 mg dl(-1). The diagnosis of insulinoma was then assumed; CT scan showed a hypodense mass into the pancreatic tail, and a partial pancreasectomy was performed. The described symptoms disappeared, and 5 years later the findings of a complete clinical and neurophysiological examination were negative. The clinical picture of insulinoma presenting with paroxysmal disorders has been previously described; however, whereas hypersomnia is uncommon, in the current case it represents the main symptom. Clinicians should keep in mind that neuroglycopenia should be considered in the differential diagnosis of patients with hypersomnia, particularly if the clinical scenario does not conform to standard criteria.